# Developing synthetic RNA organelles for spatiotemporal separation, control, and monitoring in living cells

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $382,801

## Abstract

Project summary
Our understanding of biology is being transformed by the discovery and characterization of
organelles arising from the spontaneous phase separation of proteins and RNA, in the absence
of a lipid membrane. These membraneless organelles, also called condensates, occur at different
cellular locations and can appear as solids, gels, or liquids. Dozens of distinct biomolecular
condensates are associated with pathways that regulate genes, stress response, and, and their
function depends on the types of molecules they recruit from the cellular environment. This has
spurred the interest toward developing means to harness condensation by building artificial
condensates, that could be used for separating molecules in vitro and as organelles inside living
cells. Most efforts in this direction rely on engineered proteins that include disordered domains:
this approach however is hampered by difficulties in building proteins presenting well-defined
interactions, minimal promiscuity, and limited side effects. These challenges can be addressed
by adopting engineered RNA, rather than proteins, as a building block for artificial condensates,
because specific RNA-RNA interactions are easy to program, and RNA is a molecule easily
portable across organisms presenting low toxicity.
This project aims to develop a new class of artificial condensates by taking advantage of
nanostructured RNA. We will build RNA condensates capitalizing on our recent discovery that
star-shaped RNA motifs (nanostars), comprising a single molecule of RNA, can produce dense
RNA droplets in cell-free samples and in living cells. By bridging concepts in phase separation
science and RNA nanotechnology, our project will establish RNA nanostars as a platform to build
customizable RNA organelles through different research focus areas aimed at: (1) developing
methods for sequence and structure optimization, leading to condensates with desired
thermodynamic and biophysical properties, and with specific affinity for separating guest
molecules; (2) gaining control over the location, kinetics, and composition of RNA organelles
forming inside cells; (3) establishing means to build RNA condensates that can sense and
respond to molecular signals, and explore their usefulness as sensing and imaging tools. By
providing a tunable platform to control the spatial and temporal distribution of target molecules
within living cells, our synthetic organelles will serve as a powerful tool toward achieving control
of gene expression and biosensing.

## Key facts

- **NIH application ID:** 10951551
- **Project number:** 1R35GM155833-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Elisa Franco
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $382,801
- **Award type:** 1
- **Project period:** 2024-09-25 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10951551

## Citation

> US National Institutes of Health, RePORTER application 10951551, Developing synthetic RNA organelles for spatiotemporal separation, control, and monitoring in living cells (1R35GM155833-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10951551. Licensed CC0.

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